Premium
Omega‐3 and omega‐6 fatty acids can differentially modulate signaling involved in prostaglandin synthesis
Author(s) -
Wang Lei,
Lim EunJin,
Zheng Yuanyuan,
Toborek Michal,
Hennig Bernhard
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a737
Subject(s) - phospholipase a2 , prostaglandin , chemistry , signal transduction , arachidonic acid , prostaglandin e2 , prostaglandin h2 , fatty acid synthase , phospholipase , atp synthase , biochemistry , enzyme , biology , endocrinology
The biosynthesis of prostaglandin E 2 (PGE 2 ) involves three enzymatic reactions including phospholipase A 2 (PLA 2 ), cyclooxygenase (COX), and PGE 2 synthase. We have demonstrated that linoleic acid (LA, omega‐6 18:2) can potentiate inflammatory events such as COX‐2 up‐regulation induced by TNF‐alpha. Conversely, alpha‐linolenic acid (ALA, omega‐3 18:3) protected against this effect. To test the hypothesis that LA and ALA can differentially modulate PGE 2 synthesis signaling, endothelial cells were pretreated with LA or ALA followed by exposure to TNF‐alpha. Compared to control or LA treatment, ALA decreased TNF‐alpha‐induced activation of p38 mitogen‐activated protein kinase and this effect was associated with the decreased phosphorylation of cytosolic PLA 2 . Furthermore, ALA pretreatment attenuated TNF‐alpha‐induced PGE 2 synthase expression. PGE 2 synthase is a membrane associated protein and COX‐2 has been shown to interact with caveolin‐1 (Cav‐1). We further demonstrated that both TNF‐alpha and LA increased Cav‐1 protein level, while ALA down‐regulated TNF‐alpha‐induced Cav‐1 expression. These results indicate that, although LA and ALA are not direct bioactive substrates for PGE 2 synthesis as are their 20‐carbon derivatives, the presence of 18‐carbon omega‐6 or omega‐3 fatty acids can efficiently modulate cytokine induced PGE 2 signaling. (Supported by grants from NIEHS/NIH, USDA, KY AES)